subchapter c -- federal hazardous substances act regulations

16 CFR Ch. II (1–1–05 Edition) – proposed modification – 6/25/06
Positive” in the EPA guidelines on male
reproductive risk assessment.
(ii) Probable Human Male Reproductive
Toxicant. A substance is considered a
”probable human male reproductive toxicant”
if there is ”limited” human evidence or
”sufficient” animal evidence to establish a
causal association between human exposure
and the adverse effects on male reproductive
main endpoints. This category is comparable
to the one termed ”Probable Positive” in the
EPA guidelines on male reproductive risk
assessment. However, the EPA category is
based only on sufficient animal evidence.
CPSC believes that limited human evidence is
also sufficient for a chemical to be placed in
this category.
(iii) Possible Human Male Reproductive
Toxicant. A substance is considered a
”possible human male reproductive toxicant”
if there is limited animal evidence, in the
absence of human data, or in the presence of
inadequate human data, or which does not fall
into any other group, to establish a causal
association between human exposure and
adverse effects on male reproductive main
endpoints. This category is comparable to the
one termed ”Possible Positive A” in the EPA
guidelines on male reproductive risk
assessment. EPA proposes to use either limited
human or limited animal evidence data to
classify a toxicant as a ”Possible Positive A”
toxicant. As described above, CPSC would
elevate limited human evidence to the category
”Probable Human Male Reproductive
Toxicant.”
(4) Female Reproductive Toxicants.
Female reproductive toxicants can be grouped
into the following different categories based
on evidence obtained from human or animal
studies. EPA has proposed guidelines for
assessing female reproductive risk but has not
yet proposed a specific system for
categorization of female reproductive
toxicants.
(i) Known Human Female Reproductive
Toxicant. A substance is considered a ”known
human female reproductive toxicant” if there
is ”sufficient” human evidence to establish a
causal association between human exposure
and adverse effects on female reproductive
function such as mating ability, fertility, and
prenatal and postnatal development of the
conceptus.
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(ii) Probable Human Female Reproductive
Toxicant. A substance is considered a
”probable human female reproductive
toxicant” if there is ”limited” human evidence
or ”sufficient” animal evidence to establish a
causal association between human exposure
and adverse effects on female reproductive
function.
(iii) Possible Human Female Reproductive
Toxicant. A substance is considered a
”possible human female reproductive toxicant”
if there is ”limited” animal evidence, in the
absence of human data, or in the presence of
inadequate human data, or which does not fall
into any other group, to establish a causal
association between human exposure and
adverse effects on female reproductive
function.
(d) Germ Cell Mutagenicity. Substances
are toxic by reason of their germ cell
mutagenicity when they are known to induce
heritable mutations or regarded as if they
induce heritable mutations in the germ cells of
humans.
(1) Known Germ Cell Mutagenicity
Substances. Substances are known to induce
heritable mutations in the germ cells of
humans based on positive evidence from
human epidemiological studies.
(2) Substances regarded as if they induce
heritable mutations in the germ cells of
humans. Substances should be regarded as if
they induce heritable mutations in the germ
cells of humans based on:
• Positive result(s) from in vivo heritable
germ cell mutagenicity tests in mammals; or
• Positive result(s) from in vivo somatic cell
mutagenicity tests in mammals, in
combination with some evidence that the
substance has potential to cause mutations to
germ cells. This supporting evidence may, for
example, be derived from
mutagenicity/genotoxic tests in germ cells in
vivo, or by demonstrating the ability of the
substance or its metabolite(s) to interact with
the genetic material of germ cells; or
• Positive results from tests showing
mutagenic effects in the germ cells of humans,
without demonstration of transmission to
progeny; for example, an increase in the
frequency of aneuploidy in sperm cells of
exposed people.
(3) Other Considerations. Conclusions
about heritable effects in human germ cells